Abstract
While the role of hyperhomocysteinemia in cardiovascular pathogenesis continuously draws attention, deficiency of hydrogen sulfide (H(2)S) has been growingly implicated in cardiovascular diseases. Generation of H(2)S is closely associated with the metabolism of homocysteine via key enzymes such as cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). The level of homocysteine and H(2)S is regulated by each other. Metabolic switch in the activity of CBS and CSE may occur with a resultant operating preference change of these enzymes in homocysteine and H(2)S metabolism. This paper presented an overview regarding (1) linkage between the metabolism of homocysteine and H(2)S, (2) mutual regulation of homocysteine and H(2)S, (3) imbalance of homocysteine and H(2)S in cardiovascular disorders, (4) mechanisms underlying the protective effect of H(2)S against homocysteine-induced vascular injury, and (5) the current status of homocysteine-lowering and H(2)S-based therapies for cardiovascular disease. The metabolic imbalance of homocysteine and H(2)S renders H(2)S/homocysteine ratio a potentially reliable biomarker for cardiovascular disease and development of drugs or interventions targeting the interplay between homocysteine and H(2)S to maintain the endogenous balance of these two molecules may hold an even bigger promise for management of vascular disorders than targeting homocysteine or H(2)S alone.